Newswise, December 29, 2015– More than 375,000 American each
year experience a heart attack, during which blood flow to a part of the heart
is impeded by blocked arteries.

Physicians often treat patients with stents,
which prop open the arteries to allow blood to flow again.

They use two approaches
to place stents: transradial, or entry of the catheter which delivers the stent
through the wrist, or transfemoral, in which the catheter is placed through the
groin. In a comparison of bleeding complications and mortality between the two
approaches, researchers from the Perelman School of Medicine at the University of
Pennsylvania found that those at risk for more bleeding were often
treated with a riskier procedure – the transfemoral approach – a demonstration
of the so-called risk-treatment paradox.

The findings, from the largest study
of its kind, are detailed in this week’s Journal of the American
College of Cardiology: Cardiovascular Interventions.

The subject of the study, known as rescue percutaneous
coronary intervention (PCI), is performed when a patient’s heart attack has not
subsided after being treated with powerful clot-busting medications, an
approach commonly used in developing countries and rural areas of the United
States where access to catheterization labs are not immediately available.

Researchers gathered data on 9,494 patients from the National Cardiovascular
Registry’s CathPCI database and analyzed records for those who underwent rescue
PCI between 2009 and 2013.

The findings revealed that transradial rescue PCI was only
used in about 15 percent of the rescue PCI cases performed in the United
States, and bleeding was reduced in these cases.

The team also found that
patients who were most prone to bleeding – as determined by a 33-category risk
model which accessed clinical features such as age, body mass index,
preexisting heart failure, and peripheral vascular disease – were more likely
to be treated via transfemoral access, which is known to result in more
significant post-procedure bleeding.

Of the 1,348 transradial cases analyzed,
only 93 patients experienced a bleeding complication.

However in the 8,146
treated with transfemoral PCI, 967 had significant post-procedural bleeding, a
five percent difference between the two groups.

“We were surprised to see how few of these rescue PCI cases
were approached with transradial access, given the increase in bleeding one
might expect when performing a procedure on a patient who recently received
thrombolytic therapy,” said the study’s senior author, Jay Giri, MD,
MPH, an assistant professor of Clinical Cardiovascular Medicine.

“Even more
interesting was the finding that among the group studied, patients at the
highest risk for bleeding – those who would benefit most from transradial
access – were least likely to receive that procedure. This counterintuitive
finding is a demonstration of the ‘risk-treatment paradox,’ showing that
doctors in these cases made treatment decisions based on what they are most
comfortable with rather than what is best for the patient.”

The risk-treatment paradox describes a situation in which
patients who are at the highest baseline risk for a condition are less likely
to be treated aggressively for that condition. In the present case, the authors
note that this finding may have been driven by decision-influencing factors
such as physician training or experience.

Despite differences in bleeding rates, researchers found that
there was no significant difference in mortality rates – a less than one
percent variance. In addition, the team only evaluated cases where the patient
was in stable condition following the clot-busting medication.

Therefore,
high-risk patients – those in need of assistive heart pumps – with a higher
risk of death were not included in the analysis.

Giri added that until 2004, few transradial PCI procedures
were performed in the United States, and little research was available to
demonstrate its efficacy.

“However, in recent years, both research and
widespread education in the technique has led to exponential growth in its
use,” he noted. “I would expect that over the next few years, transradial PCI
will become the standard for heart attack patients, and these results help to
further define best practices in its use.”

Penn Medicine is one of the world's leading academic medical
centers, dedicated to the related missions of medical education, biomedical
research, and excellence in patient care. Penn Medicine consists of the Raymond
and Ruth Perelman School of Medicine at the University of Pennsylvania(founded
in 1765 as the nation's first medical school) and the University of
Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top
five medical schools in the United States for the past 17 years, according to
U.S. News & World Report's survey of research-oriented medical schools.

The
School is consistently among the nation's top recipients of funding from the
National Institutes of Health, with $409 million awarded in the 2014 fiscal
year.

The University of Pennsylvania Health System's patient care
facilities include: The Hospital of the University of Pennsylvania and Penn
Presbyterian Medical Center -- which are recognized as one of the nation's top
"Honor Roll" hospitals by U.S. News & World Report -- Chester
County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and
Pennsylvania Hospital -- the nation's first hospital, founded in 1751.
Additional affiliated inpatient care facilities and services throughout the
Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn
Partners, a partnership between Good Shepherd Rehabilitation Network and Penn
Medicine.

Penn Medicine is committed to improving lives and health
through a variety of community-based programs and activities. In fiscal year
2014, Penn Medicine provided $771 million to benefit our community.

Newswise, December 29, 2015 — Researchers long have known that
some portion of the risk of developing cancer is hereditary and that inherited
genetic errors are very important in some tumors but much less so in others.

In a new analysis, researchers have shed light on these
hereditary elements across 12 cancer types — showing a surprising inherited
component to stomach cancer and providing some needed clarity on the
consequences of certain types of mutations in well-known breast cancer
susceptibility genes, BRCA1 and BRCA2.

The study, from Washington University School of Medicine in
St. Louis, appears Dec. 22 in the journal Nature Communications.

The investigators analyzed genetic information from more than
4,000 cancer cases included in The Cancer Genome Atlas project, an initiative funded
by the National Institutes of Health (NIH) to unravel the genetic basis of
cancer.

“In general, we have known that ovarian and breast cancers
have a significant inherited component, and others, such as acute myeloid
leukemia and lung cancer, have a much smaller inherited genetic contribution,”
said senior author Li Ding, PhD, associate professor of medicine and assistant
director of the McDonnell Genome Institute at Washington University.

“But this
is the first time on a large scale that we’ve been able to pinpoint gene
culprits or even the actual mutations responsible for cancer susceptibility.”

The new information has implications for improving the
accuracy of existing genetic tests for cancer risk and eventually expanding the
available tests to include a wider variety of tumors.

These studies uncovered
mutations present in the tumors, helping researchers identify important genes
that likely play roles in cancer. But this type of analysis can’t distinguish
between inherited mutations present at birth and mutations acquired over the
lifespan.

To help tease out cancer’s inherited components, the new study
adds analysis of the sequencing data from the patients’ normal cells that
contain the “germline” information.

A patient’s germline is the genetic
information inherited from both parents. This new layer of information gives a
genetic baseline of a patient’s genes at birth and can reveal whether
cancer-associated mutations were already present.

In all the cancer cases they analyzed, the investigators
looked for rare germline mutations in genes known to be associated with cancer.

If one copy of one of these genes from one parent is already mutated at birth,
the second normal copy from the other parent often can compensate for the
defect.

But individuals with such mutations are more susceptible to a so-called
“second hit.” As they age, they are at higher risk of developing mutations in
the remaining normal copy of the gene.

“We looked for germline mutations in the tumor,” Ding said.
“But it was not enough for the mutations simply to be present; they needed to
be enriched in the tumor — present at higher frequency. If a mutation is
present in the germline and amplified in the tumor, there is a high likelihood
it is playing a role in the cancer.”

In 114 genes known to be associated with cancer, they found
rare germline mutations in all 12 cancer types, but in varying frequencies
depending on the type. They focused on a type of mutation called a truncation
because most truncated genes can’t function at all.

Of the ovarian cancer cases the investigators studied, 19
percent of them carried rare germline truncations. In contrast, only 4 percent
of the acute myeloid leukemia cases in the analysis carried these truncations
in the germline.

They also found that 11 percent of the stomach cancer cases
included such germline truncations, which was a surprise, according to the
researchers, because that number is on par with the percentage for breast
cancer.

“We also found a significant number of germline truncations in
the BRCA1 and BRCA2 genes present in tumor
types other than breast cancer, including stomach and prostate cancers, for
example,” Ding said. “This suggests we should pay attention to the potential
involvement of these two genes in other cancer types.”

The BRCA1 and BRCA2 genes
are important for DNA repair. While they are primarily associated with risk of
breast cancer, this analysis supports the growing body of evidence that they
have a broader impact.

“Of the patients with BRCA1 truncations in
the germline, 90 percent have this BRCA1 truncation enriched
in the tumor, regardless of cancer type,” Ding said.

Genetic testing of the BRCA1 and BRCA2 genes
in women at risk of breast cancer can reveal extremely useful information for
prevention. When, for example, the genes are shown to be normal, there is no
elevated genetic risk of breast cancer.

But if either of these genes is mutated
in ways that are known to disable either gene, breast cancer risk is
dramatically increased. In this situation, doctors and genetic counselors can
help women navigate the options available for reducing that risk.

But mutations come in a number of varieties. Genetic testing also
can reveal many that have unknown consequences for the function of these genes,
so their influence on cancer risk can’t be predicted.

To help clarify this gray area in clinical practice, Ding and
her colleagues Jeffrey Parvin, MD, PhD, professor and director of the division
of computational biology and bioinformatics at The Ohio State University, and
Feng Chen, PhD, associate professor of medicine at Washington University,
investigated 68 germline non-truncation mutations of unknown significance in the BRCA1 gene.

For each mutation, they tested how well the BRCA1 protein could perform one of
its key DNA-repair functions. The researchers found that six of the mutations
behaved like truncations, disabling the gene completely.

These mutations also
were enriched in the tumors, supporting a likely role in cancer.

“It is important to be able to show that these six mutations
of unknown clinical significance are, in fact, loss-of-function mutations,”
Ding said.

“But I also want to emphasize the contrasting point. Many more show
normal function, at least according to our analysis. Many of these types of
mutations are neutral, and we would like to identify them so that health-care
providers can better counsel their patients.”

Ding said more research is needed to confirm these results
before they can be used to advise patients making health-care decisions.

“Our strategy of investigating germline-tumor interactions
provides a good way to prioritize important mutations that we should focus on,”
she said. “For the information to eventually be used in the clinic, we will
need to perform this type of analysis on even larger numbers of patients.”

This work was supported by the National Institutes of Health
(NIH), including the National Cancer Institute (NCI), grants R01CA180006,
R01CA178383, R01CA141090 and PO1CA101937; the National Human Genome Research
Institute (NHGRI), grants U01HG006517, R01HG007069, U54HG003079 and T32
HG000045; the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), grant R01DK087960; the Department of Defense, grant PC130118; a
Ministry of Education in Taiwan Fellowship, and CMB training grant GM 007067.
The Cancer Genome Atlas (cancergenome.nih.gov) was the source of primary data.

Washington University School of Medicine’s 2,100 employed and
volunteer faculty physicians also are the medical staff of Barnes-Jewish and
St. Louis Children’s hospitals.

The School of Medicine is one of the leading
medical research, teaching and patient-care institutions in the nation,
currently ranked sixth in the nation by U.S. News & World Report. Through
its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the
School of Medicine is linked to BJC Health

Research Findings Could Lead to Diagnostics and
Treatment for the Eye Disease

Newswise, December 29, 2015 — In one of the latest examples of precision
medicine, teams of geneticists from nine countries, involving more than 100
scientists, analyzed the genes of more than 33,000 individuals in the hope of
finding genetic variations responsible for age-related macular degeneration
(AMD), the leading cause of vision loss among people age 50 or older.

Their research, involving complex computational analysis of
more than 12 million genetic variations across the human genome, identified 52
variations associated with the disease.

By identifying these genetic variations, spread across 34 gene
regions, scientists are a step closer to developing diagnostics that identify
which patients are at high risk for acquiring the disease and formulating
therapeutics either to prevent or treat the disease caused by these genetic
variations.

Leading the coordination of the massive, multi-national
research effort conducted by the International AMD Genomics Consortium was Case
Western Reserve University School of Medicine’s Jonathan L. Haines, PhD, whose
team also helped guide the complex computational analysis of the data from
those study participants with advanced AMD and those without AMD.

Their findings appear in the December 15 edition of Nature
Genetics.

“The enormity and complexity of studying the genetics behind
AMD required a large-scale computational analysis study of the disease that
could only be performed by bringing together the world’s leading researchers,” said
Haines. Haines is the chair of Epidemiology and Biostatics and the Mary W.
Sheldon, MD, Professor of Genomic Sciences, as well as the director of the
Institute for Computational Biology—a joint venture between Case Western
Reserve University, University Hospitals Case Medical Center and Cleveland
Clinic.

As part of their research, consortium investigators chose to
study both common and rare genetic variations. Genetic variations are the DNA
sequence differences between individuals. Genetic variations affect physical
traits such as eye color or susceptibility to specific diseases.

Because of the
millions of genetic variations present in the genome, it took genetic
computational analysis from multiple centers to pinpoint the variations
specific to AMD.

Using sophisticated computer programs, scientists were able to
sort and synthesize more than 12 million genetic variations culled from the
study’s more than 33,000 individual participants.

Moreover, they applied another dynamic big data science
technique -- computational pathway analysis -- whereby statistically
significant variations are grouped together based on the genes they are
associated with and the biological pathways those genes affect.

Computational pathway analysis reveals how these gene
variation groupings may affect biological events leading to AMD.

The combined computational analysis of the entire consortium
identified, for the first time, a genetic variant specific to one subtype of
AMD. The group identified one genetic variant located near the MMP9 gene region
that is implicated only in the particularly damaging wet form of AMD.

AMD comes in dry and wet forms. Both damage vision by
destroying cells in the macula, the small center of the retina in the back of
the eye. It’s the macula’s job to focus images coming through the eye, which
are then converted to electrical signals and sent through the optic nerve to
the brain.

Localized inflammation in the retina triggers the development
of drusen, which are fatty, lipid-rich deposits that accumulate in the eye as a
natural part of the aging process.

Enough inflammation and drusen accumulation
will destroy photoreceptors in the back of the eye that receive the electrical
signals from the retina, causing vision loss.

Dry AMD causes loss of cells in the macula and progresses more
slowly. The wet form progresses rapidly and causes an abnormal growth of blood
vessels within the macula.

These blood vessels impair vision by leaking fluid into the
eye and are the result of uncontrolled vascular endothelial growth factor
(VEGF) spurring development of new blood vessels.

The consortium’s big-data solution paid off when they found
genetic variations in the region near the MMP9 gene that exclusively affect the
wet form of AMD. What MMP9 does is trigger VEGF to produce blood vessel growth
in the eye.

The finding suggests an explanation for why anti-VEGF therapy is
not as effective in many AMD patients whose genetic make-up with the MMP9 gene
variation makes them more susceptible to the disease’s progression. MMP9-induced
VEGF production might overwhelm the anti-VEGF therapy’s effect.

“Almost every study up until now has only looked at common
variations that are pervasive in the population,” said a lead author Jessica N.
Cooke Bailey, PhD, a post-doctoral fellow in the School of Medicine’s
Department of Epidemiology and Biostatics.

“Our robust big data techniques
allowed us to look for the rare variations that occur, for example, in one in
1,000 individuals. In the genetics world, those really rare genetic variations
are important because those significantly increase the risk of a disease such
as AMD in individuals who have them.”

Additionally, the consortium’s study located 10 variations
pointing to genes involved in maintaining the extracellular matrix within the
eye.

The matrix is made up of nonliving material among cells that provides
structural support in the eye. Seven of these 10 variations affecting the
extracellular matrix point to a wet AMD subtype with no early-stage symptoms
and with rapid progression.

“The possible connection between AMD and these extracellular
matrix genes may allow for predictive genetic tests and more effective
therapies for people with this type of AMD," Cooke Bailey said.

As for future research, next steps will be functional
mechanistic studies to determine why and how key gene variations activate to
cause AMD.

“More than 10 million Americans are affected by AMD,” Cooke
Bailey says.

“More than 2 million individuals over the age of 50 have the
advanced disease. AMD also adds billions of dollars to health care costs. With
more people entering their senior years, the AMD-affected population will only
continue to grow, which makes this research particularly crucial.”

The study was funded in part by NEI Intramural Research
Program and by NEI grants EY023164, EY012118, EY022310, T32 EY023194,
P30-EY005722, EY0022005, EY016862, and EY022310. The study also was supported
by NIH National Human Genome Research Institute grants HG006513, HG007022, and
1U01HG006389; National Institute on Aging grants AG019085; and National Center
for Advancing Translational Sciences grant UL1TR000427. Dr. Cooke Bailey is
supported in part by a PhARMA Informatics Postdoctoral Fellowship.

Newswise, December 29, 2015– A
team of researchers from Stony Brook University, led by Yusuf Hannun, MD, the
Joel Strum Kenny Professor in Cancer Research and Director of the Stony Brook
University Cancer Center, have found quantitative evidence proving that
extrinsic risk factors, such as environmental exposures and behaviors weigh
heavily on the development of a vast majority (approximately 70 to 90 percent)
of cancers.

The finding, reported in the December 16 online issue of Nature,
in a paper titled “Substantial contribution of extrinsic risk factors to cancer
development,” may be important for strategizing cancer prevention, research and
public health.

Inspired by a January 2015 research paper in Science, which concluded that the majority of the
variation in cancer risk among tissues is due to “bad luck,” the Stony Brook
team used the same data to assess what leads to the risk of developing cancer.

The interdisciplinary team of researchers from the Departments of Applied
Mathematics and Statistics, Medicine, Pathology and Biochemistry, concluded the
opposite – that most cancers are the result of external risk factors.

“Cancer is caused by mutations in the DNA of cells, which
leads to uncontrolled cell growth instead of orderly growth. But the
development of cancer is a complex issue, and we as a scientific community need
to have solid analytical models to investigate what intrinsic and extrinsic
factors cause certain forms of cancer,” said Dr. Hannun, senior author of the
paper.

“Many scientists argued against the ‘bad luck’ or ‘random
mutation’ theory of cancer but provided no alternative analysis to quantify the
contribution of external risk factors,” explained Song Wu, PhD, lead author of
the paper, and Assistant Professor in the Department of Applied Mathematics and
Statistics, Stony Brook University.

They developed four distinct approaches to assess cancer risk.
With these four approaches, they discovered collectively and individually that
most cancers are attributed largely to external risk factors, with only
10-to-30 percent attributed to random mutations, or intrinsic factors.

First, the researchers examined extrinsic risks by tissue cell
turnover. In a data-driven approach, they re-examined the quantitative
relationship between observed lifetime risk of cancer (ie, for lung,
pancreatic, colorectal and other tissues) and division of the normal tissue
stem cells in those groups reported in the Science paper.

If intrinsic risk
factors played a major role, the tissue with the similar stem cell divisions
would show similar observed lifetime cancer risk. They found this pattern to be
a rare one, and thus determined intrinsic factors played a vital role in only
about 10 percent of cancers.

These results are supported by strong
epidemiologic evidence; for example studies showing that immigrants moving from
countries with lower cancer incidence to countries with higher rates of cancer
incidence acquire the higher risk in their new country.

The researchers also mathematically surveyed and analyzed
recent studies on mutational signatures in cancer, which are regarded as
“fingerprints” left on cancer genomes by different mutagenic processes.

Some 30
distinct signatures among various cancers were identified. They analyzed the
signatures and categorized them as having intrinsic or extrinsic origins.

They
found that while a few forms of cancer had a greater than 50 percent of intrinsic
mutations, the majority of cancers, such as colorectal, lung, bladder and
thyroid cancers had large proportions of mutations likely caused by extrinsic
factors.

The team also analyzed the SEER (Surveillance, Epidemiologic
and End Results Program) data, which showed that many cancers have been
increasing in incidence and in mortality, suggesting that external factors
contribute heavily to these cancers.

Lastly, they used computational modeling to dissect the
contribution of the intrinsic processes in the development of cancer, based on
known gene mutations in cancer and the likelihood that they arise from
intrinsic mutation rates.

They found that when three or more mutations are
required for cancer onset (which is a currently accepted parameter), intrinsic
factors are far from sufficient to account for the observed risks, indicating
small percentages of intrinsic cancer risks in many cancers.

The four methods involved both data- and model-driven
quantitative analyses, with and without using the stem cell estimations. The
idea behind the overall approach was to assess cancer risk by multiple methods
and not by a single type of analysis.

Dr. Hannun concluded that their overall approach “provides a
new framework to quantify the lifetime cancer risks from both intrinsic and
extrinsic factors, which will have important consequences for strategizing
cancer prevention, research and public health.”

Co-authors of the paper include: Scott Powers of the
Department of Pathology at Stony Brook University, and Wei Zhu, of the
Department of Applied Mathematics and Statistics at Stony Brook University.

All
of the authors are collaborating investigators at the Stony Brook University
Cancer Center.

About Stony Brook University
Part of the State University of New York system, Stony Brook University
encompasses 200 buildings on 1,450 acres. Since welcoming its first incoming
class in 1957, the University has grown tremendously, now with more than 25,000
students and 2,500 faculty.

Its membership in the prestigious Association of
American Universities (AAU) places Stony Brook among the top 62 research
institutions in North America. U.S. News & World Report ranks Stony Brook
among the top 100 universities in the nation and top 40 public universities,
and Kiplinger names it one of the 35 best values in public colleges.

One of
four University Center campuses in the SUNY system, Stony Brook co-manages
Brookhaven National Laboratory, putting it in an elite group of universities
that run federal research and development laboratories. A global ranking by
U.S. News & World Report places Stony Brook in the top 1 percent of
institutions worldwide.

It is one of only 10 universities nationwide recognized
by the National Science Foundation for combining research with undergraduate education.
As the largest single-site employer on Long Island, Stony Brook is a driving
force of the regional economy, with an annual economic impact of $4.65 billion,
generating nearly 60,000 jobs, and accounts for nearly 4 percent of all
economic activity in Nassau and Suffolk counties, and roughly 7.5 percent of
total jobs in Suffolk County.

Newswise, December 29, 2015--A drug that boosts activity in
the brain’s “garbage disposal” system can decrease levels of toxic proteins
associated with Alzheimer’s disease and other neurodegenerative disorders and
improve cognition in mice, a new study by neuroscientists at Columbia
University Medical Center (CUMC) has found.

The study was published today in
the online edition of Nature Medicine.

“We have shown for the first time that it’s possible to use a
drug to activate this disposal system in neurons and effectively slow down
disease,” said study leader Karen E. Duff, PhD, professor of pathology and cell
biology (in psychiatry and in the Taub Institute for Research on Alzheimer’s
Disease and the Aging Brain) at CUMC and at the New York State Psychiatric
Institute.

“This has the potential to open up new avenues of treatment for
Alzheimer’s and many other neurodegenerative diseases.”

The drug used was
rolipram, which causes nausea and thus is not a good drug for use in humans,
but similar drugs do not incur nausea as a side effect and could go into
clinical trials very quickly.

To remain healthy, brain cells must continually clear out old,
worn, or damaged proteins, a task performed by a small molecular cylinder
called the proteasome.

The proteasome acts as a kind of garbage disposal,
grinding up the old proteins so they can be recycled into new ones. In
neurodegenerative diseases, proteins tagged for destruction accumulate in the
brain’s neurons, suggesting that the cell’s proteasomes are impaired.

Using a mouse model of neurodegeneration, the researchers
first discovered that tau--a toxic protein that accumulates in Alzheimer’s and
other brain degenerative diseases--sticks to the proteasome and slows down the
protein disposal process.

Administering rolipram activated the proteasome and restored
protein disposal to normal levels. The drug also improved the memory of
diseased mice to levels seen in healthy mice.

Rolipram has been tested before in mice and was shown to
improve memory, but the mechanism for how this occurred was unclear. The new
research shows that by inhibiting of the PDE-4 enzyme, rolipram produces a
physical change in the proteasome that increases its activity.

“We still don’t know exactly where the activation is
happening, but what’s new is that we can modify the proteasome to increase its
activity. There could be many other ways to do this,” said the study’s first
author, Natura Myeku, PhD, an associate research scientist in pathology and
cell biology at CUMC.

Drugs that target proteasomes in this way should work for any
disease caused by the accumulation of abnormal proteins, including Alzheimer’s,
Huntington’s, Parkinson’s and frontotemperoral dementia.

“Treatments that speed up these cell disposal mechanisms
should, in theory, only degrade abnormal proteins. We don’t need to know what
the toxic form of the protein is,” Dr Duff said.

“In Alzheimer’s disease, there
are at least four different types: amyloid, tau, alpha-synuclein, and TDP43. A
well-functioning proteasome can clear out everything at once.”

“This exciting research from Dr. Duff’s team advances our
basic understanding of the proteasome system, provides a way to repair the
system when it breaks, and alleviates symptoms of neurodegenerative disorders,”
said Rod Corriveau, PhD, program director at the National Institute of Health’s
National Institute of Neurological Disorders and Stroke, which provided funding
for the study.

The study is titled, “26S proteasome dysfunction and cognitive
impairment caused by aggregated tau accumulation can be attenuated by
PKA-mediated phosphorylation of proteasomes.”

The study was supported by grants from the National Institute
of Neurological Disorders and Stroke (NS074593), the CurePSP Foundation, the
National Institute of General Medical Sciences (GM051923), the Fidelity
Biosciences Research Initiative, and the Multiple Myeloma Research Foundation.

The researchers declare no financial or other conflicts of
interest.

The Taub Institute for Research on Alzheimer’s Disease and the
Aging Brain at Columbia University Medical Center is a multidisciplinary
group that has forged links between researchers and clinicians to uncover the
causes of Alzheimer’s, Parkinson’s, and other age-related brain diseases and to
discover ways to prevent and cure these diseases.

It has partnered with the
Gertrude H. Sergievsky Center at Columbia University Medical Center, which was
established by an endowment in 1977 to focus on diseases of the nervous system,
and with the Departments of Pathology & Cell Biology and of Neurology to
allow the seamless integration of genetic analysis, molecular and cellular
studies, and clinical investigation to explore all phases of diseases of the
nervous system. For more information, visit The Taub Institute at www.cumc.columbia.edu/dept/taub/.

Columbia University Medical
Center provides international leadership in basic, preclinical, and clinical
research; medical and health sciences education; and patient care. The medical
center trains future leaders and includes the dedicated work of many physicians,
scientists, public health professionals, dentists, and nurses at the College of
Physicians and Surgeons, the Mailman School of Public Health, the College of
Dental Medicine, the School of Nursing, the biomedical departments of the
Graduate School of Arts and Sciences, and allied research centers and
institutions. Columbia University Medical Center is home to the largest medical
research enterprise in New York City and State and one of the largest faculty
medical practices in the Northeast. For more information, visit www.cumc.columbia.edu or www.columbiadoctors.org

Wednesday, December 23, 2015

Newswise, December 23, 2015 — According to the Centers for
Disease Control and Prevention, each year approximately 2.1 million patients in
the Emergency Department are transferred to an intensive care unit. When that
happens, relatives are also impacted and need a support system, according to
Loyola University Health System (LUHS) licensed clinical social worker Kelly
McElligott.

“Families are totally unprepared for a sudden injury and
overwhelmed when it is a very serious injury,” says McElligott. “Families need
a roadmap to guide them through their worst moments, and that is my job as a
hospital social worker.”

McElligott works in Loyola’s Burn Center, the largest burn
center in Illinois and nationally renowned for treating the most complex
wounds. “Our average length of stay is about three weeks but we have many
patients who are with us for several months, due to the severity of their
condition,” says McElligott.

“The patients and their families have at their disposal a
multidisciplinary team of physical therapists, dietitians, psychologists,
chaplains and social workers. We all work together with the traditional care
team of surgeons, physicians and nurses.” Loyola pioneered the integrated care
model that is emulated by hospitals internationally.

Here are McElligott’s top tips for adults who find a loved one suddenly in the
hospital:

Take care of yourself. “If you do not take care of yourself,
you cannot take care of someone else,” says McElligott. “Many family members,
especially parents, feel they need to be at the hospital 24/7 with their loved
one,” she says. “Everyone needs to take time to eat, sleep, exercise and be
with other people in the outside world.”

When one member is in the hospital, it is important for the
whole family to continue to move forward. “Life does not stop because someone
is in the hospital. Other family members need attention and support also,” she
says.

“Mom and Dad need to be role models more than ever at this
time. The hospital team can help support and guide them. And they can feel
strengthened and confident to continue to guide their families.”

Accept help from your community. “Friends, relatives,
colleagues and others will offer assistance and it is critical to accept help,”
says McElligott.

“For example, coming home to a clean house and a meal in the
refrigerator is very convenient and also comforting.” Online programs can be
useful helpmates, such as those that coordinate meal organization, task and
errand running, and communication with family.

“Many times, key family members are reluctant to ask or
receive help. Usually there are outgoing neighbors or colleagues who will serve
as primary contacts to relieve the burden,” says McElligott.

“People feel better when they have something to do; let them
help and everyone will benefit.”

Ask a lot of questions. “Nurses, physicians, social workers
and all medical staff are here to answer questions and offer resources,” says
McElligott. “No individual could know what to expect when a severe injury
occurs. That’s what medical professionals are for.”

Use a notepad or laptop and take notes when meeting with your
health team. “Write down questions or concerns as they come to you and share
them with your care team,” she says. “As they say in school, there are no bad
questions, so do not feel shy or embarrassed. The more you know, the less you
will fear.”

Talk to others about your experience. “Reach out to people for
support by sharing your experience or what you have witnessed,” says McElligott.
“Often, this will help reduce anxiety and build confidence.”

Sharing your story is often difficult and emotional at first,
but becomes easier over time. “Talking helps define the event or injury, remove
the emotion and perceived stigma, and can help identify next steps to move
forward,” she said. “Getting feedback from others also can be reassuring and
supportive.”

Use peer support. “Others who have walked the path you are on
offer invaluable support, insight and understanding,” says McElligott. For
example, Loyola offers a bi-monthly burn support group for patients and their
families. “Speakers are brought in to share specific expertise but the greatest
benefit comes through the informal talking among families,” she says.

Former burn patients are frequent visitors to the hospital
floor and visit with patients and their families. “There are amazing stories of
patients and family members who are very withdrawn and depressed who respond
positively to our former burn patient volunteers,” she says. “They are able to
see that life does go on, there are others who survived much worse injury and
are still laughing, socializing and enjoying life.”

McElligott says it is a privilege to meet patients and their
families during one of the worst times of their lives, and to guide them
through the recovery process.

“People are very resilient,” she says. “The transformations that happen once
the shock wears off are amazing.”

Newswise,
December 23, 2015– Poor cognitive function is a serious problem in the aging
HIV-positive population, where it has been estimated that up to 59 percent of
HIV-positive adults demonstrate at least mild cognitive impairment.

University
of Alabama at Birmingham School of Nursing Assistant Professor Shannon
Morrison, Ph.D., is exploring multiple effects of a ketogenic diet — a
high-fat, low-carbohydrate diet with adequate protein — in medically stable,
older persons living with HIV who have mild to moderate neurocognitive
impairment.

The
study, following previous encouraging research, is supported by a one-year,
$60,000 grant from the UAB Center for Clinical and Translational Science.

“In the
studies that have been conducted so far, the ketogenic diet has shown some
promising results in improving cognition in other neurocognitive disorders,”
Morrison said.

“We’re hoping to see if the same or similar results will occur
to the older, cognitively impaired HIV population. I am just thrilled at this
opportunity and am preparing to begin recruitment in early January.”

A person
consumes fewer than 50 total grams of carbohydrates per day on a ketogenic
diet. When the amount of carbohydrates, or sugars, the body has to process for
fuel is limited, it will start to break down fat and, as a byproduct of that
fat metabolism, produce the ketones for which the ketogenic diet is named.

“What a
ketogenic diet does is change the energy source the body uses for fuel for its
activities,” Morrison said.

“If you are not taking in much sugar, your body
will start breaking down fat for energy, and a byproduct of the fat metabolism
is ketone bodies. The body, including the brain, is then able to efficiently
utilize ketone bodies for energy.”

This
randomized control trial, “The Effect of a Ketogenic Diet on HIV-Associated
Neurocognitive Impairment,” will compare the effects of a 12-week ketogenic
diet versus a patient-choice diet on cognitive function and cardiovascular
risks in 20 older persons with stable HIV disease.

This study is a part of the
National Center for Advancing Translational Sciences of the National Institutes
of Health.

For this
pilot study, half the participants will be randomly assigned to the ketogenic
diet group and half to the patient-choice diet group.

Baseline data will be
collected as the starting point to look for changes that may be linked to
improved cognitive function similar to what has been seen in people with other
neurological disorders, including Alzheimer’s disease, Parkinson’s disease and
epilepsy, who ate a ketogenic diet.

In addition, five members of the ketogenic
group will undergo functional magnetic resonance imaging after 12 weeks to
examine changes in neural activity associated with consumption of a ketogenic
diet.

“The
ketogenic diet has shown to decrease systemic inflammation in Alzheimer’s and
Parkinson’s diseases, as well as after a cerebral vascular injury and traumatic
brain injury in patients,” Morrison said.

“We hope that the ketogenic diet will
reduce systemic inflammation that may reduce heart and diabetes risks as well
as improve cognitive performance in HIV-positive individuals.”

Throughout
the 12-week trial, those in the ketogenic diet group will be provided meals and
snacks. The meals will be matched for energy content to maintain current energy
balance and will consist of less than 50 grams of carbohydrates per day with
the participants’ daily carb intake coming primarily from non-starchy, fresh
vegetables.

Morrison
hopes the results of this study will lead to a larger clinical trial down the
road and ultimately to solutions that will help improve neurocognitive
performance in older HIV-positive patients.

“We hope
to find ways to help these individuals function more independently without
adding more medication for them to take but rather through an improved diet,”
she said.

December
23, 2015--A network of interacting brain regions known as the default mode
network (DMN) was found to have stronger connections in adults and children
with a high risk of depression compared to those with a low risk.

These
findings suggest that increased DMN connectivity is a potential precursor, or
biomarker, indicating a risk of developing major depressive disorder (MDD).

The study
was published online today in Neuropsychopharmacology.

Researchers
at Columbia University Medical Center (CUMC) and New York State Psychiatric
Institute (NYSPI) used magnetic resonance imaging to compare people at high
risk for depression to those at low risk based on their family history of
depression.

This
approach allowed researchers to look for differences in the brain that are not
a consequence of the depression itself, since the disorder had not yet
manifested in most of the individuals.

The DMN
brain system is more active when people are focused on internal thinking, such
as ruminative thoughts.

Increased
DMN connections have previously been seen in individuals with MDD, may relate
to ruminative symptoms, and typically normalize with antidepressant treatment.
The study reveals that the process of increasing DMN connections may occur
before the onset of depression.

“These
findings suggest that looking at activity in the DMN may offer an objective
method of identifying people who are at risk of developing major depression,”
said lead author Myrna Weissman, PhD, the Diane Goldman Kemper Family Professor
of Epidemiology (in Psychiatry) at CUMC and Chief of the Division of
Epidemiology at NYSPI.

“This may
represent a another way toward advancing prevention and early intervention for
this major public health issue.”

“If this
insight proves correct,” said Jonathan Posner, MD, lead author and Associate
Professor of Clinical Psychiatry at CUMC, ”behavioral interventions that
improve the functioning of the DMN, such as meditation and mindfulness, could
be used to address a brain-based problem (increased DMN connections), before it
leads to a depressive illness.”

The
article, entitled “Increased Default Mode Network Connectivity in Individuals
at High Familial Risk for Depression,” was published online as an accepted
article preview in Neuropsychopharmacology; doi:
10.1038/npp.2015.342. The authors are Jonathan Posner, Jiook Cha, Zhishun Wang,
Ardesheer Talati, Virginia Warner, Andrew Gerber and Myrna Weissman at the
College of Physicians and Surgeons, Columbia University, New York, NY, USA; New
York State Psychiatric Institute, New York, NY, USA; and Bradley S Peterson at
the Institute for the Developing Mind, Children’s Hospital Los Angeles and the
Keck School of Medicine, University of Southern California, Los Angeles, CA,
USA.

This study was supported in part by NIMH grants R01-MH036197 and K23-MH091249
and the Sackler Institute for Psychobiology

Dr Posner
has received research support from Shire Pharmaceuticals. The remaining authors
have no competing interests to report.

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About Me

Daniel Hines is an international-award winning communicator with extensive experience as a senior-level communications executive with some of America’s leading corporations, and as the founder of his own communications consulting business since 1986. A graduate of Bradley University, where he was elected to the Phi Kappa Phi honor society for scholastic excellence, he has established TodaysSeniorsNetwork as a leading source of information for issues affecting an Aging America, as well as advocacy on behalf of successful aging. He is also a leading spokesperson and advocate on behalf of access by Americans to safe, affordable, personally imported prescription medicines as a bulwark against the predatory pricing practices of Pharma.